Induction of a mucosal immune response will be an essential attribute of a successful vaccine to block transmission of HIV infection. Studies in the SIV animal model system have demonstrated that immune responses following mucosal exposure to viral vectors and peptides can blunt the replication and pathogenesis of SIV after infection. Viral vectors based on two members of the poliovirus and coxsackievirus have been employed in some of these studies. The use of these and similar enteroviruses is attractive, as they replicate in lower gastrointestinal tract, and are likely to produce immune responses in both the gastrointestinal and genital tracts. However, safety concerns and plans to completely curtail the circulation of poliovirus are likely to dampen enthusiasm for using these specific viruses as vaccine vectors. The parechoviruses are closely related, but biologically distinct picornaviruses that appear naturally attenuated relative to coxsackie and polioviruses strains employed to date. Of particular importance, serious complications of parechovirus have been only rarely reported, even after infection of infants. We propose to construct and complete the initial in vitro testing of a parechovirus based vaccine vector, based on strategies already employed in the successful construction of enteroviral vectors.